Apparatus and methods for transferring materials between locations possessing different cross-sectional areas with minimal band spreading and dispersion due to unequal path-lengths

ABSTRACT

Non-limiting exemplary embodiment(s) of apparatus(es) and method(s) are described for the conveyance of fluid media and entrained materials between two or more locations, each possessing a different cross-sectional area. Equidistant pathways incorporated into uniquely designed conduits enable this transference to occur with minimal band spreading and separation resolution loss due to undesirable flow patterns that arise from end effects. The design enables the conduits to be employed with locations of almost any description including process channels, surfaces, or even open volume of any size and used for almost any purpose. The conduits and/or associated locations may be empty of any contents or filled with gelatinous, porous, granular, or particulated material. The design of non-limiting exemplary embodiment(s) of apparatus(es) and method(s) may be easily adapted or configured as necessary.

CROSS REFERENCE TO RELATED APPLICATIONS

Not Applicable.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

REFERENCE TO A MICROFICHE APPENDIX

Not Applicable.

BACKGROUND OF THE INVENTION

1. Technical Field

This application relates generally to fluid distribution. Morespecifically, the application provides apparatuses that enable fluid andsample particles to be uniformly distributed and collected to and fromprocess channels, surfaces, or open volumes with minimal dispersion.

2. Prior Art

Many analytical and engineering processes use fluids to transport bandsof material or samples between locations. In most, if not all, of theseapplications, it is important to keep spreading, skewing, and mixing ofthe bands to a minimum. As the materials move through the fluid handlingsystems, they can be subjected to dispersion resulting from diffusion,turbulent mixing, and non-uniform flow velocities. Unintended andundesirable hydrodynamic dispersion and stagnation can lead to materialdilution, a blurring of the boundaries between adjacent bands, andunpredictable transit rates. Instead of distinct bands, there is a lossof separation resolution as materials arrive in a progressive mannerover an extended period of time. In analytical and synthetic systems, itbecomes difficult to reliably deliver precise concentrations of multiplereagents to specific locations at predetermined times and sequences.High throughput is most easily achieved when material or sample bandsare closely spaced without significant dispersion during transportthrough the fluid handling system.

Such dispersion is often exacerbated when systems are miniaturized.There has been great interest in recent years in down-sizing analyticaland reactor systems as the potential of micro- and nano-fluidic devicesand technology to provide robust, highly accurate, high throughput, andlow cost methodology has become more evident. “Lab-on-a-chip” platformshave been developed that enable sampling, separation, control,transport, mixing, incubation, reaction, and analysis, sometimes allwithin a single integrated device. As these systems become more complex,however, greater attention must be paid to possible sources ofinadvertent band spreading.

In the late 1990s and early 2000s, a number of investigators studiedturns and junctions (wyes and tees) in two-dimensional microscalesystems and developed methods to minimize dispersion from these sources.Kopf-Sill and Parce (U.S. Pat. No. 5,842,787), for example, recommendusing a channel turn geometry where the depth of the channel is greaterthat its width. The narrower width helps reduce dispersion caused by adifference in path length (and thus transit time) along the inner andouter walls of a turn, the so called “racetrack effect.” Furtherreduction in dispersion is suggested by fabricating the turn with thedepth along the inner radius greater than that of the outer to reduceflow velocity along the inner radius. Microfluidic channels withvariable depths, however, are difficult to manufacture and therefore arecostly. Again recognizing the advantage of narrow channels, Paegel etal. (2000) recommend a “pinched turn” design in which the channel widthis reduced prior to the turn and then expanded back to the originalwidth once the turn is complete. In a similar manner, Griffiths andNilson (U.S. Pat. No. 6,270,641) advise that the contraction andexpansion regions actually be incorporated into the turn itself. Thiswork is extended to include 45, 90 and 180 degree turns, wyes, and tees,as well as sample splitting devices and serpentine channels for foldinglong columns into small areas. Not all systems, however, require adramatic alteration to the structure. Culbertson et al. (1998) pointsout that under certain circumstances the skewing of material caused by aturn can often be partially reversed by simply following the first turnwith a second turn in the opposite direction. The extent to which theskewing can be reversed depends on the diffusivity of the particles inthe particular fluid medium and the distance between the turns.

Another concern is the dispersion that can occur as fluid passes betweenregions of different cross-sectional areas in the flow system. Suchtransitions occur, for example, at inlet and outlet ports on separationchannels or reaction chambers where the orifice at the ports may beorders of magnitude smaller than the width of the channel or chamber. Asfluid medium with any entrained samples emerges from the inlet tubeunder laminar flow conditions, it fans out to the full width of thechannel. The spreading fluid produces a crescent-shaped fluid front thatpersists as the fluid progressively moves along the length of channel.At the other end of the channel, the fluid medium and sample particlesthen funnel from across the width into the outlet tubing. As aconsequence, sample particles follow flow paths of varying lengthsthrough the channel. A particle on a direct line between the inlet andoutlet along the center of the channel travels a significantly shorterdistance than one that first diverges from the inlet to the channel'swidth before converging at the outlet end. The resulting path inequitieslead to a spreading of sample particles away from each other and thusband broadening. Since the transitions between the differentcross-sectional areas are generally at the ends of the channel orchamber, these flow non-uniformities and the resulting dispersion areoften referred to as “end effects.”

Numerous suggestions have been proposed in the literature to lessen theinfluence of end effects on separation resolution. Most begin byincorporating a wedge-shaped (triangular) zone between the inlet oroutlet port and the main body of the channel or chamber. With the portlocated at the apex of the triangle, the more gradual transition helpsminimize the introduction of flow stagnation or turbulence into fluidsmoving through the transition. Using this design for example, Giddingset al. (1984) illustrated that the variation in sample path lengththrough the channel and thus the dispersion can be reduced by simplyminimizing the apex angle on the triangular transitional section. Thework found reasonably good correlation between chromatographictheoretical plate height calculations and visual studies that examinedthe shape of the fluid flow profile using methylene blue samples in anoptically transparent glass channel. In a second, more comprehensiveinvestigation, Williams et al. (1986) mathematically corroborated theearlier work by employing conformal mapping techniques to generatetheoretical equipotential curves, flow streamlines, and associated flowprofiles as a function of apex angle.

Improvements in resolution, however, often come with tradeoffs andlimitations. On close examination of the experimental and theoreticalprofiles, Williams et al. (1986) pointed out that, although reducing theapex angle decreased the end effect, it also unavoidably increased therelative contribution of the “edge effect” to the distortion of thefluid flow profile. The edge effect is a slowing of the fluid near theside walls of the channel. Photographic images of methylene blue samplesin channels possessing large apex angles displayed the expectedcrescent-shaped flow profile compromised only by a small degree oftailing at the side walls of the channel, presumably due to edgeeffects. Since these tails incorporate only a very small fraction of thezonal material, their influence on the final flow profile is small. Inchannels with smaller apex angles, however, images showed significanttailing and departure from simple end effect calculated flow profiles.Williams et al. (1986) conjectured that the divergence could beattributed to the fact that the zonal material was in greater contactwith the side walls for a longer distance. Edge effects generally becomemore prominent as the thickness of the channel increases. The ability toimprove separation resolution by simply altering the apex angletherefore appears to be limited by the need to balance the deleteriousconsequences of the two (end and edge) effects. These studies byGiddings and Williams clearly show that reducing the apex angle in thetransitional triangular section between regions of differentcross-sectional areas is not by itself sufficient to eliminate thedispersion and resolution losses brought about by end effects.

Another method suggested for reducing end effects-associated bandbroadening was to reduce the volume of the transitional triangularsection. From one perspective, the triangular sections can be thought ofas being external to the main channel or chamber. Chromatographic theoryhas shown that the dispersion introduced by an external volume isproportional to the square of the volume. Two different approaches havebeen used to reduce the volume of the transitional section. The firstwas proposed by Giddings et al. (1984) and involved adjusting thethickness of the triangular section to about one-fourth that of areference channel. This volume reduction work, which was done inconjunction with their apex angles studies, was performed using whatmight be considered a macroscale system. The channel had a width of 6centimeters. Using a somewhat different approach, Sant et al. (2006)designed a flow system that incorporated an array of microstructuralcolumns into the transitional sections. The logic here was that thecolumns would not only decrease the effective volume of the triangularsections, but would also redistribute the flow streams in a way thatminimized differences in flow path lengths. To optimize results, thestudy examined a variety of microstructure geometries andconfigurations. Both experimental work and simulations were performed.This investigation, however, was done at a more microscale level using achannel with a width of only 3.5 millimeters. Interestingly, despite thesize differential, both approaches resulted in decreased dispersion dueto end effects and produced about a 50% reduction in the theoreticalplate height when compared to their respective reference channels.

As indicated above, improvements in resolution, however, often come withtradeoffs and limitations. Sant et al. (2006) pointed out that furtherreduction in band broadening may ultimately be limited by increases inlocal edge effects that result from the presence of the microstructures.Consideration must also be given to the dramatically increased surfacearea provided by the columns and the increased possibility ofintermolecular interaction with sample particles. Both approachesincrease the complexity of the flow system and add another challenge tothe manufacturing process. No commercially available flow system orinstrument has incorporated either of the volume-reduction approaches.

Although the investigations by Giddings, Williams, and Sant were allconducted on channels employed in field-flow fractionation (FFF)separations, much of their work is adaptable to other techniques (bothmacro and micro) and helps illustrate the difficulties associated withdesigning devices to circumvent dispersion introduced by changes incross-sectional area. Field-flow fractionation is a single-phaseelution-based particle separation and characterization techniquegenerally performed in a narrow, flat, rectangularly-shaped,ribbon-like, separation channel typically formed from two closely spacedparallel or concentric surfaces with inlet and outlet ports located ateither end. The relatively simple configuration of the FFF channel andthe extensive theoretical development of the FFF separation processreadily facilitate the transfer of design considerations from FFF toother flow systems.

In 2006, Cummings and Fiechtner (U.S. Pat. No. 7,005,301) recommended anentirely different approach to dispersion reduction employingelectrokinetic flow in microfluidic systems. Rather than directlyaddressing the inequality of flow path lengths associated with theracetrack and end effects as discussed above, their technique alters thedirection of fluid flow by passing the flow across an abrupt interfacebetween two regions possessing different specific permeabilities.Specific permeability is a quantity the authors define with dimensionsof length, instead of the more commonly applied property ofpermeability, which has units of area. The system is constructed from aseries of straight, open channels called “faceted flow prisms,” eachpossessing a predetermined specific permeability established by thedepth and width of the channel. The ends of a channel are cut atpredetermined angles. In connecting two channels together, the actualangle used on each channel is determined by the dimensions of thechannel and the directional change to be brought about in the flow. Bycontrolling the angle, interfacial contact area, and specificpermeabilities of two connecting channels, the authors indicate that awide range of turning angles and expansion ratios are possible withminimal dispersion. The system is modular in design, allowing thecomponent prisms to be connected in an array of different configurationsincluding transitions between regions of different cross-sectionalareas.

The methodology developed by Cummings and Fiechtner is designedspecifically for microfluidic applications and assumes the presence ofideal electrokinetic flow. Unlike pressure-driven flow which produces aparabolic profile and a velocity that depends on the size of channel,the velocity profile for electrokinetic (electroosmotic) flow is flatand the velocity is independent of the channel dimensions.Electrokinetic techniques, however, also exhibit some significantdrawbacks. Electroosmotic flow is not particularly robust and is highlysensitive to the physicochemical properties of the solution and channelwalls. When used with real samples, care must be taken to insure thatsolute molecules do not adsorb onto channel walls (often unavoidable anduncontrollable) creating inhomogeneities in surface charge density andlocal areas of flow anomalies. The need for an electrically conductivesolution with tightly controlled pH and ionic strength generally makesthe technique inapplicable to non-aqueous media or the use of solutiongradients. Unfortunately, the composition of the conductive solution canbe influenced by the electrochemical reactions at the system'selectrodes that are used to maintain the required electric field insolution. High operating voltages (1-30 kV power supply) resulting inhigh currents in solution can also bring about runaway Joule heating andthe need for cooling.

Other concerns about the faceted prism approach are its scalability andthe manufacturing precision required to achieve the desired decrease indispersion. Because each faceted interface introduces a small amount ofdispersion, there is also a practical upper limit to the number ofinterfaces that can be coupled together. Using electrokinetic flowalone, it is difficult to extend the methodology for microscale channelsto handle macroscale systems. Studies by Skulan et al. (2005), however,have found that velocity variations along faceted interfaces usingpressure-driven flow can be unacceptable for many applications.Additional dispersion can be introduced by flow velocity inequitiesresulting from rounded corners and inexact interfacial angles andchannel depths incurred during channel fabrication.

Although novel approaches have been developed to lessen the impact ofend effects on band spreading, few of the methods are currently used ona regular basis, and none totally eliminate the problem. Without asolution, however, high resolution, high throughput separations andtransfer processes are difficult to achieve. The problem, in fact, isbecoming even more acute as new preparative scale applications move towider channels to provide higher load capacity and analytical worktrends towards smaller microscale systems to minimize analysis time andthe amount of sample and fluid medium required. Since the relativecontribution of end effects to separation inefficiency dramaticallyincreases as the channel becomes either shorter or wider, end effectsultimately limit channel dimensions. It would therefore be ofsubstantial interest and benefit to develop apparatuses with associatedmethodologies that would enable the uniform distribution and collectionof materials and samples to and from process channels, surfaces and openvolumes without the dispersion and resolution losses introduced by theend effects associated with transitions across regions of differentcross-sectional area.

The present invention is directed to overcoming one or more of theproblems and solving one or more of the needs as set forth above.

BRIEF SUMMARY OF THE INVENTION

The present invention provides apparatuses and methods for the uniformtransference of fluid media and any entrained materials or samplesbetween two or more locations possessing different cross-sectionalareas. What is unique is that the transference is done without theintroduction of significant band spreading and dispersion. The locationsmay be associated with enclosed volumes, surfaces, or even open spaces.Material, for example, might be collected from narrow-bore tubing at onelocation and dispensed as a uniform, long, thin band across a flatsurface at a second location. Alternatively, the process may bereversed. Material flowing in an open space might be uniformly sampledthrough a long, narrow, rectangularly-shaped input orifice andtransferred to a small cross-sectional pipe or duct. In either case, thepresent invention enables closely spaced materials to arrive at a secondlocation from a first with minimal dispersion or loss of resolutionbetween the samples.

Two or more embodiments of the invention may also be placed at eitherend of a closed volume. Embodiments, for example, are particularlyapplicable to the delivery and collection of fluid media and materialsto and from channels or chambers dimensioned to possess a high aspectratio (width/thickness). Such channels may be employed to house a widerange of processes including chemical reactions, mixture separations,sample detection or characterization, and the like. The channel may beopen, filled with gel, or filled with porous, granular, or particulatedmaterial. Such process channels may also be of any shape, althoughrectangular is common. The apparatuses and methods are designed tominimize the introduction of dispersion and separation resolution lossesregardless of the size of the system, whether macro- or microscale.

Typical process channels are connected to other components in theprocess system with transfer lines that generally possess a much smallercross-sectional area than the channel itself. A traditional channel insuch a system might therefore be envisioned as being fabricated toinclude three distinct sections: a main section where the actual processoccurs and two transitional sections (one incorporated at each end ofthe main section) that guide the movement of fluid medium and anyentrained materials or samples to the main section from the channel'sinlet and away from the main section to the channel's outlet. Generally,these transitional sections are triangular in shape.

End effects are flow nonuniformities and distortions that originatewithin the transitional sections. As material/sample particles in thefluid medium fan out from the inlet of the transitional area, generallythe apex of a triangle (substantially a point), the distance traveled byindividual particles will vary depending on exactly where the particlecrosses along the interfacial boundary line between the transitionalarea and main section of the channel. Material/sample particles near thecenter of the interfacial line travel a shorter distance than those nearthe ends. These path-length inequities cause a spreading ofmaterial/sample particles away from each other (band broadening ordispersion) and thus a loss of separation resolution. The presentinvention replaces the transitional sections of the traditional processchannel with apparatuses and methods that substantially eliminate thepath-length and flow nonuniformities associated with end effects.

Each embodiment of the apparatuses for the present invention comprises aconduit of predetermined shape having two ends, one end having a smallportal of predetermined size and dimensions and the other end having alarge portal of predetermined size and dimensions. The shape of theinterior of the conduit is designed in such a way that the length of thepath through the conduit is essentially the same from the small portalon the one end of the conduit to anywhere within the dimensions of thelarge portal on the other end. Each embodiment is provided with a meansby which fluid medium (possibly containing entrained materials and/orsamples) may be either introduced into or collected from the smallportal in the conduit. To function in a flow system, a means is providedto connect the large portal of the conduit to the end of the mainsection of a process channel. The embodiments are used in lieu of thetraditional transitional sections. A simple channel assembly may beconfigured, for example, by connecting one embodiment at each end of arectangularly-shaped main section. With the channel arranged in thisway, fluid medium and sample particles travel into the small portal onone embodiment, through the main section of the channel, and out of thesmall portal in the second embodiment. Since the length of all pathsthrough the channel from the small portal at one end to the small portalat the other is essentially the same, the channel eliminates the flownonuniformities and distortions that generally originate within thetriangular areas of the traditional process channel. Theembodiment-incorporated channel provides less dispersion and greatermaterial/sample separation resolution than a comparably dimensionedprocess channel of the more traditional design.

The design of the apparatuses in the present invention may take manyforms. In some embodiments, the hollow space within the conduit may be asingle entity with a small portal at one end to connect to inlet oroutlet tubing and a large portal at the other end of the conduitdimensioned to fit the opening in the main section of channel to whichit is to be attached. In other embodiments, the conduit may besubdivided into multiple entities, each originating at a common smallportal. The openings at the other end of the entities collectivelyconstitute the large portal and are configured as a unit to fit thedimensions of the main section of channel to which the conduit is to beattached. In either the single or subdivided case, the path lengththrough the conduit from the small portal on the one end of the conduitto anywhere within the dimensions of the opening or openings that makeup the large portal at the other end of the conduit are essentially thesame.

The shape and configuration of the conduit in a particular embodimentdepend on the process system into which it is to be incorporated and thespecific application for which the system is to be used: Embodiments maybe open, filled with gel, or filled with porous, granular, orparticulated material. Embodiments may be fabricated as a continuouspart of the main section of the channels or designed to be readilydisconnected and/or disassembled for ease in cleaning or replacement.Construction materials and techniques may be selected to accommodatealmost any sample and/or choice of fluid medium. Where required,embodiments may provide multiple simultaneous input and/or outputconnections to a single main section of the channel. The overall sizeand alignment of embodiments may be adjusted to the requirements ofalmost any process system. The present invention is particularlyeffective when incorporated into “lab-on-a-chip” microscale andmanufacturing preparative macroscale process systems, applications wheretraditional process channels are most susceptible to end effect bandspreading and resolution losses.

Non-channel applications of the invention include uses where samplematerial is collected from surfaces or open volumes. Designed with along, narrow large portal, embodiments of the invention can uniformlysample across a conveyer of moving material collecting only a verynarrow band of material. Such a capability is desirable when trying todiscriminate between closely spaced longitudinally placed samples orincrements along the conveyer. The apparatus might be used to sample thebands on an electrophoresis gel, for example, or the strata in avertical collected ice or sediment core. Alternatively the invention maybe used to deposit sample materials onto surfaces or into open volumes.Some applications are best performed employing two embodiments of theinvention coupled to function in unison. One embodiment uniformlysupplies fluid medium to a surface to dissolve, dislodge, or extractsample material while an adjacent second embodiment collects thedissolved, dislodged, or extracted material for transport to subsequentprocessing.

The embodiments and procedures included in the following descriptions ofthe present invention are given to illustrate the basic principles andversatility of the invention, and are not intended to limit the scope ofthe invention. Each embodiment was chosen to demonstrate a particularcapability of the present invention to circumvent or dramatically reducethe end effect problems that are associated with the traditionalchannels typically used in most process systems.

There has thus been outlined, rather broadly, the more importantfeatures of the invention in order that the detailed description thereofthat follows may be better understood, and in order that the presentcontribution to the art may be better appreciated. There are additionalfeatures of the invention that will be described hereinafter and whichwill form the subject matter of the claims appended hereto.

It is noted the purpose of the foregoing abstract is to enable the U.S.Patent and Trademark Office and the public generally, especially thescientists, engineers, and practitioners in the art who are not familiarwith patent or legal terms or phraseology, to determine quickly from acursory inspection the nature and essence of the technical disclosure ofthe application. The abstract is neither intended to define theinvention of the application, which is measured by the claims, nor is itintended to be limiting as to the scope of the invention in any way.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

The novel features believed to be characteristic of this invention areset forth with particularity in the appended claims. The inventionitself, however, both as to its organization and method of operation,together with further objects and advantages thereof, may best beunderstood by reference to the following description taken in connectionwith the accompanying drawings in which:

FIG. 1A shows a simplified isometric representation of a traditionalhigh aspect ratio (width/thickness) channel as may be found in priorart.

FIG. 1B shows a simplified cross-sectional representation of atraditional high aspect ratio (width/thickness) channel as may be foundin prior art. The view is looking at the width of the channel throughthe thickness and perpendicular to the fluid medium flow.

FIG. 2A shows the extent of longitudinal band spreading that can occurin a traditional high aspect ratio channel from prior art. The apexangle is equal to 30 degrees.

FIG. 2B shows the extent of longitudinal band spreading that can occurin a traditional high aspect ratio channel from prior art. The apexangle is equal to 60 degrees.

FIG. 2C shows the extent of longitudinal band spreading that can occurin a traditional high aspect ratio channel from prior art. The apexangle is equal to 90 degrees.

FIG. 3 shows a generalized block representation of an overall approachto an apparatus that incorporates two embodiments of the presentinvention.

FIG. 4A shows an exploded view of one embodiment of a conduit connectedto both end of the main section of a process channel.

FIG. 4B shows the same process channel as in FIG. 4A, except in FIG. 4Bthe components are assembled together and shown from a more isometricperspective.

FIG. 5 shows the components of a model that can be used to explain theoperating principles underlying one embodiment of the conduit.

FIG. 6 shows typical values for the apex angle as a function of thecircle radius-to-channel width ratio, r/c. FIG. 6 also shows theinfluence of the circle radius-to-channel width ratio on the relativemagnitudes of conduit dimensions and volume.

FIG. 7 shows an isometric representation of a conduit assembly accordingto one embodiment of the present invention.

FIG. 8A shows a spacer used in construction of one embodiment of aconduit assembly.

FIG. 8B shows a second spacer used in construction of one embodiment ofa conduit assembly.

FIG. 8C shows a second spacer placed over a partially assembledembodiment of a conduit assembly.

FIG. 9 shows an exploded view of one embodiment of a conduit designed tofacilitate construction using micro fabrication techniques. The conduitin FIG. 9 comprises three rectangular solid substrates (A, B and C) andone cylindrically shaped substrate (D).

FIG. 10A shows substrate D from FIG. 9 incised to include the upperportion of a conduit and an inlet tube.

FIG. 10B shows a cross-sectional view of the assembled conduit shown inFIG. 9. The view is from a perspective looking down the length of thechannel and inlet tube incised into substrates B and substrates C,respectively.

FIG. 10C shows a cross-sectional view of the assembled conduit shown inFIG. 9. The view is from a perspective looking at the side of substrateD and the side of the channel and inlet tube incised into substrates Band substrates C, respectively.

FIG. 11 shows a short channel assembly formed using two embodiments of aconduit assembly.

FIG. 12 shows a simplified schematic representation for a typical systemdesigned to supply fluid medium and sample material to a process channelassembly and then detect, analyze, and/or collect the material afterprocessing.

FIG. 13 shows a long channel assembly formed using two embodiments of aconduit assembly.

FIG. 14A shows an exploded view of components used to construct theupper portion of the conduit assembly in FIG. 13.

FIG. 14B shows an exploded view of components used to construct thelower portion of the conduit assembly in FIG. 13.

FIG. 15 shows the main section of a channel connected to an embodimentof a conduit assembly that is segmented in three areas and incorporatestwo small portals.

FIG. 16A shows a first spacer that may be employed in the constructionof the upper portion of the conduit assembly in FIG. 15 when the conduitis to be used to facilitate the introduction of fluid medium and sampleparticles into a process channel.

FIG. 16B shows a first spacer that may be employed in the constructionof the upper portion of the conduit assembly in FIG. 15 when the conduitis to be used to facilitate the collection of fluid medium and sampleparticles from a channel.

FIG. 17A shows an exploded view of components used to construct theupper portion of multiple side-by-side conduits.

FIG. 17B shows an exploded view of components used to construct thelower portion of multiple side-by-side conduits.

FIG. 18 shows a first spacer that may be used in the construction of theupper portion of the multiple side-by-side conduits in FIG. 17A.

FIG. 19A shows a channel assembly from a perspective perpendicular tofluid medium flow through the channel that provides a view across thewidth of the channel.

FIG. 19B shows examples of second and third spacers used in theconstruction of the channel assembly in FIGS. 19A and 19C.

FIG. 19C shows a channel assembly from a perspective perpendicular tofluid medium flow through the channel that provides a view across thethickness of the channel. This represents the sectional view from FIG.19A taken at section line 19C-19C.

FIG. 20A shows a channel assembly that may be used to deliver or collectfluid medium and any entrained sample material to or from a surface oropen volume.

FIG. 20B shows two adjacent channel assemblies that may be used todeliver and/or collect fluid medium and any entrained sample material toand/or from a surface or open volume.

FIG. 21 shows an embodiment fabricated using CNC machining to producethe shape of the conduit.

FIG. 22 shows a flowchart of a typical method for delivering fluidmedium and materials, with a minimum of band spreading and dispersiondue to edge effects, from a first location to a second locationpossessing a different cross-sectional area

FIG. 23 shows a flowchart of a typical method for collecting fluidmedium and materials, with a minimum of band spreading and dispersiondue to edge effects, from a second location to a first locationpossessing a different cross-sectional area

Those skilled in the art will appreciate that the figures are notintended to be drawn to any particular scale; nor are the figuresintended to illustrate every embodiment of the invention. The inventionis not limited to the exemplary embodiments depicted in the figures.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will now be described more fully hereinafter withreference to the accompanying drawings, in which a preferred embodimentof the invention is shown. This invention may, however, be embodied inmany different forms and should not be construed as limited to theembodiment set forth herein. Rather, this embodiment is provided so thatthis application will be thorough and complete, and will fully conveythe true scope of the invention to those skilled in the art. Likenumbers refer to like elements throughout the figures.

The illustrations of the embodiments described herein are intended toprovide a general understanding of the structure of the variousembodiments. The illustrations are not intended to serve as a completedescription of all of the elements and features of apparatus and systemsthat utilize the structures or methods described herein. Many otherembodiments may be apparent to those of skill in the art upon reviewingthe disclosure. Other embodiments may be utilized and derived from thedisclosure, such that structural and logical substitutions and changesmay be made without departing from the scope of the disclosure.Additionally, the illustrations are merely representational and may notbe drawn to scale. Certain proportions within the illustrations may beexaggerated, while other proportions may be minimized. Accordingly, thedisclosure and the figures are to be regarded as illustrative ratherthan restrictive.

One or more embodiments of the disclosure may be referred to herein,individually and/or collectively, by the term “present invention” merelyfor convenience and without intending to voluntarily limit the scope ofthis application to any particular invention or inventive concept.Moreover, although specific embodiments have been illustrated anddescribed herein, it should be appreciated that any subsequentarrangement designed to achieve the same or similar purpose may besubstituted for the specific embodiments shown. This disclosure isintended to cover any and all subsequent adaptations or variations ofvarious embodiments. Combinations of the above embodiments, and otherembodiments not specifically described herein, will be apparent to thoseof skill in the art upon reviewing the description.

The Abstract of the Disclosure is provided to comply with 37 C.F.R.§1.72(b) and is submitted with the understanding that it will not beused to interpret or limit the scope or meaning of the claims. Inaddition, in the Detailed Description, various features may be groupedtogether or described in a single embodiment for the purpose ofstreamlining the disclosure. This disclosure is not to be interpreted asreflecting an intention that the claimed embodiments require morefeatures than are expressly recited in each claim. Rather, as thefollowing claims reflect, inventive subject matter may be directed toless than all of the features of any of the disclosed embodiments. Thus,the following claims are incorporated into the Detailed Description,with each claim standing on its own as defining separately claimedsubject matter.

The below disclosed subject matter is to be considered illustrative, andnot restrictive, and the appended claims are intended to cover all suchmodifications, enhancements, and other embodiments which fall within thetrue scope of the present invention. Thus, to the maximum extent allowedby law, the scope of the present invention is to be determined by thebroadest permissible interpretation of the following claims and theirequivalents, and shall not be restricted or limited by the foregoingdetailed description.

For clarity in presenting and understanding the present invention, thefollowing definitions are provided. Unless defined otherwise, alltechnical and scientific terms used herein have the same meaning as iscommonly understood by one of ordinary skill in the art to which thisinvention belongs. All patents, applications, and scientificpublications cited in any section of this application are incorporatedherein in their entirety. If a definition set forth in this section iscontrary to or otherwise inconsistent with a definition set forthelsewhere in the patent or scientific literature incorporated byreference herein, the definition set forth in this section prevails.

The term “conduit” as used herein shall refer to an enclosed space orpassageway that facilitates the movement of fluid medium and anyentrained sample material from one location to another location. Theconduit includes at least one small portal at one end and at least onelarge portal at the other end. The small and/or large portal may bedesignated as an inlet or outlet port. The shape of the conduit is suchthat the length of the path through the conduit from the small portal toanywhere within the large portal is substantially the same. The smalland large portals may be subdivided into smaller subsections. Theconduit may be totally empty and open or filled (entirely or partially)with materials or objects that may alter the flow of fluid medium and/orsample materials through the channel. The objects, for example, may bean array of posts or columns randomly or systematically arranged withinthe conduit. Alternatively, the conduit may be filled or packed withporous or non-porous media such as beads or micro- or nano-particulatematerials, or frits, or porous sol-gels, or fibers or yarns, or thelike, or any combination thereof. To use the conduit for its intendedpurpose, a means is provided for moving fluid medium and sampleparticles to or from the small portal in the conduit. A means is alsoprovided for conveying fluid medium and sample particles from or to thelarge portal in the conduit to or from a channel, a device, a surface,or other designated area or volume.

The term “conduit assembly” as used herein shall refer to the physicalstructure that encloses and defines the size and shape of the conduit.

The term “channel” or “process channel” as used herein shall refer to anenclosed space or volume having a thickness, a width, and a length ofpredetermined dimensions. The channel possesses at least one openinglocated towards one end for passing fluid medium into the channel and atleast one opening located towards the other end for passing fluid mediumout of the channel. The openings may be designated as the inlet andoutlet ports, respectively. To differentiate embodiments of the presentinvention from prior art, the term “traditional channel,” “traditionalprocess channel,” or “traditionally constructed channel” as used hereinshall refer to channels that typically can be envisioned to includethree distinct sections: a main rectangular section where the actualprocess occurs and two transitional sections (one incorporated at eachend of the main section) to facilitate the movement of fluid medium andsample material between the channel's inlet and outlet ports and themain section. The “traditional” terms also apply to channels thatinclude only one transitional section and/or channels where the processin the channel occurs in both the main and transitional sections. Theterm “path-equalized channel,” or “path-equalized process channel,” asused herein shall refer to channels where the transitional section inthe traditional channel is replaced with a conduit as defined above.Also as discussed above with the conduit, the channel (eithertraditional or path-equalized) may be totally empty and open or filled(entirely or partially) with materials or objects that may alter theflow of fluid medium and/or sample materials through the channel.

The term “channel assembly” or “process channel assembly” as used hereinshall refer to the physical structure that encloses and defines thespace or volume occupied by the channel or process channel.

The term “fluid medium” as used herein shall include any gas, liquid,supercritical fluid, or mixture thereof that may be used to dissolve,disperse, or suspend the sample materials. The fluid medium may be apure substance or a mixture, inorganic or organic, polar or non-polar,an ionic liquid, or an aqueous solution. The medium may includedissolved materials to influence or control ionic strength, pH, surfacetension, or other physicochemical characteristics. The fluid medium isgenerally used to carry the sample materials through the channel and,where applicable, through peripheral instrumentation and equipment (suchas the pump, injection device, detector, connecting tubing, and thelike).

The term “sample material” or “sample particles” as used herein shallrefer to materials that may be added to the fluid medium. The materialsmay be dissolved, dispersed, suspended, or in any other form in thefluid medium. Individual particles of the material may be rigid ordeformable and range in dimension from atomic size to 100 micrometers orlarger. The materials may be singular in nature or composed ofaggregates or clusters, in any phase (solid, liquid, or gas) orcombination thereof. The materials may be regular in shape or amorphous,naturally occurring or synthetic. Although not limited to the followingexamples, this definition includes such materials as organic andinorganic macromolecules, polymers, and aggregates, nanotubes andrelated materials, emulsions and sols, micelles, dusts and powders, DNA,RNA, proteins, viruses, bacteria, plant and animal cells, cellaggregates, cell parts, and freshwater and marine organisms. Biologicalmaterials may be living or non-living.

The term “end effects” as used herein shall refer to undesirablepatterns introduced into the flow of fluid medium and sample materialsor particles while passing through the transitional sections in thetraditional process channel. The transitional sections are used tofacilitate the movement of fluid medium and sample particles between thechannel's main section and the channel's inlet and outlet ports. Asfluid medium with its entrained sample particles emerges from the inletport, it fans out to the full width of the channel. The spreading fluidproduces a crescent-shaped fluid front that persists as the fluidprogressively moves along the length of channel. At the other end of thechannel, the fluid medium and sample particles then funnel from acrossthe width into the outlet port. As a consequence, sample particlesfollow flow paths of varying length through the channel. A particle on adirect line between the inlet and outlet along the center of the channeltravels a significantly shorter distance than one that first divergesfrom the inlet to the channel's width before converging at the outletend. The resulting path inequities lead to a spreading of sampleparticles away from each other (band broadening) and a loss ofseparation efficiency and resolution. The term “end effects” may also beused herein to describe band broadening that results from pathinequities that may occur when sample particles are introduced at anypoint along the length of the channel.

The present invention is designed to provide uniform transfer of fluidmedia and any entrained materials or samples between different locationspossessing different cross-sectional areas. The transfer is made in away that minimizes the band spreading and distortion that can originatefrom flow path-length inequities. Although simple in concept, particulardetails of the invention are most easily understood when delineated inthe context of a specific application. As a means of demonstration andexplanation therefore, much of the following discussion describes theinvention as it specifically applies to the movement of fluids andmaterials to and from high aspect ratio (width/thickness) processchannels (or chambers). Such channels find broad utilization in bothlaboratory and industrial settings for processes that range from simplechemical synthesis to the separation and characterization of complexmixtures. It should be understood, however, that this application toprocess channels is only being employed as an example for illustration.The concepts described are readily adaptable to a wide variety of otherapplications. In addition to the invention's use with totally enclosedentities, the invention may also be applied to the delivery and/orcollection of fluid medium and materials to and from surfaces or evenopen space areas. The embodiments shown in FIGS. 7-20 illustrate thisflexibility.

FIGS. 1A and 1B show a traditional high aspect ratio (width222/thickness 224) channel 110 as may be found in prior art. FIG. 1A isfrom a more isometric perspective while 1B focuses on the width of thechannel. Such a channel 110 may typically be envisioned as possessingthree regions: a main section 120 where the actual process occurs andtwo transitional sections 130, one incorporated at each end of the mainsection 110. The transitional sections 130 guide the movement of fluidmedium and any entrained materials or samples to the main section 120from the channel's inlet port 180 and away from the main section to thechannel's outlet port 190. Arrow 252 shows the direction of flow throughthe channel 110. Generally, these transitional sections 130 aretriangular in shape, each with an apex angle 170, generally of equalsize. The inlet 180 and outlet ports 190 are typically located at theapices of the triangles. Line 125 indicates the position of theinterfacial boundary between the main section 120 and transitionalsection 130.

As fluid medium enters the channel 110 through inlet port 180, the fluidfollows the shape of the transitional section 130 as it fans out to thefull width 222 of the main section 120 of the channel 110. The result,as shown in FIGS. 2A-2C, is the formation of a curved arch-shaped fluidfront 160 that is subsequently maintained as the fluid medium continuesinto the main section 120. When a collection of sample particles isintroduced into the inlet port 180 as a tight plug, the sample particlesfan out in a similar arch-shaped fashion. With the vector of particlemotion split between the longitudinal and lateral directions, theforward migration of the individual particles through channel 110 is notall the same. There is a longitudinal spreading 150 of the collection ofparticles down the channel. The forward (longitudinal) distance traveledby individual particles varies depending on exactly where the particlecrosses along the interfacial boundary line 125 between the transitionalsection 130 and main section 120 of the channel. Particles near thecenter of the interfacial line 125 travel a shorter distance between theinlet port 180 and the interface 125 than those near the ends. Theextent of distance disparity depends on the size of the apex angle 170.As the size of the angle increases, the longitudinal spreading 150 alsoincreases. The apex angles 170 in FIGS. 2A, 2B, and 2C are 30, 60, and90 degrees, respectively. These path-length inequities, often called endeffects, cause a spreading (band broadening or dispersion) ofmaterial/sample particles away from each other and thus a loss ofseparation resolution.

In general then, the problem to be corrected requires that fluid mediumand materials be transferred from a first location to a second locationor vice versa without incurring end effects. FIG. 3 shows a generalizedblock representation of an overall approach to an apparatus that canprovide this transfer ability. The transfer is made through a conduit201. The conduit 201 has a predetermined shape and includes a smallportal 204 (shown in FIG. 4) of predetermined size and dimensions and alarge portal 206 (also shown in FIG. 4) of predetermined size anddimensions. The shape of the conduit 201 is such that the length of thepath through the conduit 201 from the small portal 204 to anywherewithin the large portal 206 is substantially the same. A means 270 isprovided for moving fluid medium and sample particles into or out of thesmall portal 204 in the conduit 201 from or to a first location 226. Ameans 272 is also provided for conveying fluid medium and sampleparticles from or to the large portal 206 in the conduit 201 to or froma second location 228.

FIGS. 4A and 4B show the overall approach in FIG. 3 applied to a processchannel. To circumvent the end effects problem, the transitional section130 of the traditional process channel 110 (FIG. 1B) is replaced with aconduit 201 (the present invention) configured to provide uniformdistances from end- to-end regardless of the path through the conduit.The modified channel is referred to as a path-equalized channel 100 andincorporates two conduits 201, one connected to either end of the mainsection 120 of a channel. Each conduit 201 comprises a small portal 204of predetermined size and dimensions and a large portal 206 ofpredetermined size and dimensions. The shape of the conduit 201 is suchthat the length of the path through the conduit 201 from the smallportal 204 to anywhere within the large portal 206 is substantially thesame. The connection between the large portal 206 in the conduit 201 andthe main section of the channel 120 provides the means 272 (FIG. 3) forconveying fluid medium and sample particles between the two. The mainsection of the channel 120 serves as the second location identified inFIG. 3. Inlet 25 and outlet 55 tubes, not shown in FIG. 4 but discussedin connection to FIG. 10, provides a means 270 (FIG. 3) for moving fluidmedium and sample particles into or out of the small portal 204 in theconduit 201 from or to a first location 226 (FIG. 3).

The exploded view in FIG. 4A shows the conduit 201 in two parts. Thelower part 203 of the conduit 201 has a straight edge (line 206) and acurved edge. Connection of the lower part 203 is made to the end of themain section 120 of the process channel along the straight edge. Boththe main section 120 and the lower part 203 of the conduit 201 are inthe same plane. The triangularly-shaped upper part 202 of the conduit201 projects perpendicular to that plane and is connected to the lowerpart wrapped around its curved edge. The corners of the upper part 202,lower part 203, and main section 120 all intersect. The small portal 204in the conduit 201 is located at the apex of the triangularly-shapedupper part 202. FIG. 4B shows the process channel 100 from a moreisometric perspective with the components assembled together.

A simple mathematical model will help illustrate how the conduit 201eliminates the end effects associated with traditional process channels.To avoid unnecessary complications in the calculations, a model ischosen that essentially treats the structure of the embodiment as asurface. This simplification is particularly appropriate to applicationsof the invention that involve channels or chambers of uniform thicknesswith a high aspect ratio (width/thickness) where the flow velocityacross the thickness can often be treated as a monolithic entityrepresented by a single mean value. By employing this surfaceapproximation, any analysis of flow pathways can then be restricted toonly those oriented across the width of the embodiment. Furthersimplification is also realized by neglecting any dispersion that mightbe introduced as a result of diffusion or edge effects and by assumingthat all flow velocities across the various pathways are uniform.Although more encompassing or sophisticated approaches can be taken, themodel discussed here has been found to correlate well with experimentaldata and emphasizes the ease with which embodiments can be designed andconstructed.

FIG. 4A is redrawn as FIG. 5 to better emphasize the components in themodel. The main section 120 of the path-equalized channel 100 in FIG. 4Ais represented in FIG. 5 as a rectangle 404 placed inside a circle 406in such a way that the corners of the rectangle coincide with thecircumference of the circle. The width of the rectangle 404 defines thelength of chords 410 and identifies the ends of arcs 408. Two isoscelestriangular areas 402 are wrapped around the circumference of the circleat either end of the rectangle 404 with the apices 424 of the triangularareas pointing perpendicular to the plane of the circle. In the model,the bases 418 of the triangular areas 402 are made equal to each otherand identical to the length of the arcs 408. The area between the chord410 and arc 408 in FIG. 5 corresponds to lower part 203 of the conduit201 in FIG. 4A. The triangular area 402 corresponds to upper part 202 inFIG. 4A. In a similar way, chord 410 in the model shown in FIG. 5corresponds to the large portal 206 in FIG. 4A and the small portal 204in FIG. 4A is located at the apex 424 in FIG. 5. In embodiments thatincorporate this design, fluid would enter at the apex 424 of thetriangular area 402 and flow to chord 410 which defines one end of themain section 120 of the channel 100 in FIG. 4A (represented in FIG. 5 byrectangle 404). In a similar way, fluid exiting the main section(rectangle 404) at the opposite end would flow from the second chord 410to apex 424 of the other triangular area 402. Understand that someembodiments might only incorporate the entrance or exit portion of thedesign. One of the compelling features of this model is that only simplegeometric relationships are required to calculate the parameters neededto construct most embodiments of the invention.

The calculations are approached here by first defining the width of thedesired channel (rectangle 404) and the radius 412 of the circle 406.These parameters are then used to determine the length of the arc 408and the dimensions of the adjoining triangular areas 402.

Based on the properties of intersecting chords, it can be shown that

$\begin{matrix}{{( {{2r} - h} )h} = ( \frac{c}{2} )^{2}} & {{Eq}.\mspace{14mu} 1}\end{matrix}$

where “r” is the radius 412 of the circle, “c” is the length of thechord 410, and “h” is the length of the sagitta 414, a line segmentdrawn perpendicular to the chord between the midpoint of the chord 410and the arc 408 of the circle. Sagitta 414 is determined by rearrangingEq. 1 to a quadratic form, Eq. 2, and then solved with a quadraticformula to produce Eq. 3.

$\begin{matrix}{{h^{2} - {2{rh}} + \frac{c^{2}}{4}} = 0} & {{Eq}.\mspace{14mu} 2} \\{h = {r - ( {r^{2} - \frac{c^{2}}{4}} )^{1/2}}} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

In addition, once defined, the circle radius 412 and the length of thechord 410 can also be used to determine s, the length of arc 408, which,in turn, defines the length of the bases 418 of the triangular areas402.

$\begin{matrix}{s = {2{r\lbrack {{arc}\; {\sin ( \frac{c}{2r} )}} \rbrack}}} & {{Eq}.\mspace{14mu} 4}\end{matrix}$

The remaining dimensions of the triangular area 402 are evaluated byrecognizing that dispersion due to unequal pathways will only beminimized if a uniform distance exists between apex 424 and any point onthe adjacent chord 410. With this concept in mind, a convenient way toproceed is to set two such pathways equal to each other. For example,“y”, the length of the side 416 of the triangular area should equal thesum of “x”, the height 420 of the triangular area at its center, and“h”, the sagitta 414.

y=x+h  Eq. 5

Values for “x” and “y” can then be expressed trigonometrically in termsof “c”, the length of the chord 410, “s”, the length of the arc 408, andangle “θ”, 422.

$\begin{matrix}{\frac{c}{\cos \; \theta} = {\frac{s}{2\; \tan \; \theta} + h}} & {{Eq}.\mspace{14mu} 6}\end{matrix}$

Angle “θ” can then be determined by applying an iterative approach toEq. 6, the point where the right and left hand sides of Eq. 6 becomeequal. The apex 424 of the triangular area 402 has an angle, “α”, thatis numerically twice the value of angle “θ”, 422.

α=2θ  Eq. 7

FIG. 6 shows typical values for the apex angle as a function of thecircle radius-to-channel width ratio, “r/c”. An embodiment constructedfor a channel that is 25.0 mm wide using a circle radius of 25.0 mm, a“r/c” ratio of 1.00 for example, requires an apex angle of 57.4 degrees.Ratios rather than absolute dimensions were used in constructing FIG. 6to emphasis the universal applicability of the model to almost any sizesystem, from analytical microscale to preparative macroscale. All valuesin the FIG. 6 are calculated based on assigning the chord “c” anarbitrary length of 1. In setting up the model, the length of the chord410 (FIG. 5) is the same as the width of the main section 120 of thechannel 100 (FIG. 4A).

Although geometrically any “r/c” ratio in FIG. 6 provides uniformdistances between the apex of the triangular area 402 and chord 410,laboratory test results show that other factors must also be taken intoconsideration. Neither an excessively small nor an excessively large r/cratio is desirable. Experimentally, as the r/c ratio becomes smaller,fluid medium flow exhibits a greater tendency to become unstable at highflow rates. Instability generally leads to mixing and greaterdispersion. At the other extreme, as the size of the r/c ratios becomeslarger, the overall length of the embodiment increases and the totalvolume of the structure expands. The volume almost doubles as the r/cratio is increased from 1.0 to 2.0. Experimental results show that largevoid volumes outside the main process section of the channel generallyalso contribute to an overall increase in dispersion and a loss ofseparation resolution. This dispersion is further augmented by what arecalled “edge effects.” The larger “r/c” ratios (small apex angles)contract the width of the structure providing greater contact betweenfluid medium and the structure's side walls. Fluid adjacent to the wallsmoves slower relative to the flow rate in the bulk of the fluid due tofriction or drag. The narrower the structure, the greater the variationin flow velocities and the greater the dispersion due to edge effects.The optimal configuration generally depends on the application and theoverall size of the structure. The best experimental results aretypically found at intermediate “r/c” ratios of about 1.0.

The conduit assembly is the physical structure that gives shape to theconduit. FIG. 7 shows an isometric representation of a conduit assembly200 according to one embodiment of the present disclosure viewed fromthe side that would be connected to the main section 120 of apath-equalized channel 100 (FIGS. 4A and 4B). The embodiment is easilyconstructed from readily available materials without the aid ofcomputer-assisted machining devices and is typical of a conduit thatmight be used in a macro-size (or larger micro-size) channel assembly.Other embodiments more conducive to micro- or nano-size construction arediscussed later. The conduit assembly 200 in FIG. 7 comprises threesubstrates: first 210, second 212, and third 214, described below. Eachmay be composed of a variety of solid materials including materials thatare electrically and thermally conductive, semi-conductive, ornonconductive in nature, or various composites or combinations thereof.The substrates may be singular entities, layers of the above materials,or materials covered or coated with liquid or semi-liquid substances.Aluminum, copper, glass, polymer plastics, and the like are commonlyemployed materials. The substrates may be of the same material ordifferent. For ease in construction and maintenance, the use ofoptically transparent materials is helpful.

The conduit 201 within the conduit assembly 200 is formed by fittingappropriately shaped substrates 210, 212, and 214 together separated byappropriately designed and configured spacers 217 and 218. The firstsubstrate 210 is a D-shaped solid which can easily be fabricated bycutting a cylindrical solid from end-to-end. The diameter of thecylinder and the position of the cut depend on the width of the mainsection 120 (FIG. 4A) of the channel to which the conduit assembly isultimately to be attached. To accommodate a 38 mm (1.5 inch) widechannel, for example, a 50 mm (2.0 inch) long section of 76 mm (3.0inch) diameter cylinder might be used. This would provide aradius-to-chord ratio “r/c” of 1.0 based on the model discussed inconnection with FIG. 5. The surfaces on the cylinder should be smoothand the cylinder's ends preferably flat and perpendicular to the side.The D-shaped solid is formed by cutting the cylinder end-to-end so thatthe center of the resulting surface is 5 mm (0.2 inch) from the centerof the curved edge. The cut is preferably perpendicular to the ends ofthe cylinder. The resulting surface should be rendered uniformly smoothand flat.

The second substrate 212 is a crescent-shaped solid fabricated toconform to the curvature of the first substrate 210. The secondsubstrate 212 is easily cut from a section of tubular solid. For usewith the above example, the tube might be 50 mm (2.0 inch) long with aninside diameter of about 76 mm (3.0 inch), having a wall thickness of 10mm (0.38 inch). The exact diameter depends on the flexibility of thematerial used and the thickness of the first spacer 217 that will beplaced between the first 210 and second 212 substrates. As with thecylinder, the surfaces on the tubular solid should be smooth and theends preferably flat and perpendicular to the sides. The crescent-shapedsolid is constructed by cutting the tube end-to-end in such a way thatthe arc that forms the inside surface of the tube is approximately thesame length as the curved outside surface of the first substrate 210.

The third substrate 214 is typically a flat, sheet-like rectangularsolid. A thickness of 10 mm (0.38 inch) is generally adequate to providethe necessary rigidity. The overall size should be equal to or largerthan the outermost dimensions of the second substrate 212. Preferably,third substrate 214 is shaped to match the D-shaped silhouette of thesecond spacer 218 described below.

The construction of the conduit 201 in this embodiment of the conduitassembly 200 is probably more easily described if the conduit 201 isenvisioned to have an upper portion 202 and a lower portion 203following the model described in FIG. 5. To construct the upper portion202, the inner surface of second substrate 212 is wrapped around thefirst substrate 210 with an appropriately shaped and configured firstspacer 217 in between. First spacer 217 is typically formed from sheetmaterial dimensioned to match the curved surface of the first substrate210. Its thickness is generally equal to or smaller than the thicknessof the main section 120 of the channel to which the conduit 201 is to beconnected. The material may be the same or different than thesubstrates. In one embodiment, for example, both the first 217 andsecond 218 spacers were made from 0.25 mm (0.010 inch) thick celluloseacetate film and used in conjunction with first 210, second 212, andthird 214 substrates made from PMMA, polymethyl methacrylate. To formthe upper portion 202 of the conduit 201, a triangular-shaped area iscut out of the first spacer 217 so that one side of the triangle isalong the edge of the spacer 217, as shown in FIGS. 7 and 8A, andcentered from side-to-side. For the example described above where themain section 120 of the channel is 38 mm, the base side of the cut-outtriangle should be 41 mm in length and angles at the base should each be61 degrees. The dimensions were calculated so that the distance betweenthe two corners adjacent to the edge will substantially match the 38 mmwidth of the main section 120 of the channel when the first spacer 217is wrapped around the curvature of the first substrate 210. Beforeassembling, a small hole should be made into the second substrate 212 insuch a way that the hole will be located just inside the cut-outtriangular area of the first spacer 217 when the conduit assembly 200 isassembled. This hole, which is the small portal 204 for the conduit 201,should be fitted with low-volume tubing to serve as inlet tube. (Theinlet tube 25 will be described in connection with FIG. 12.) The inlettube provides the means for moving fluid medium and sample particles toor from the small portal 204 in the conduit 201. Finally, this upperportion 202 of the conduit 201 is assembled by securely bonding thefirst spacer 217 to the curved surface of the first substrate 210 withan appropriate bonding agent or adhesive. The inner surface of thesecond substrate 212 is then bonded to first spacer 217. Care must beexercised to insure that the triangular cut-out area remains free ofbonding agent and that the edges of all three pieces align.

To form the lower portion 203 of the conduit 201, the second spacer 218is prepared having the shape shown in FIGS. 8B and 8C. FIG. 8B showsjust the second spacer 218. FIG. 8C shows the second spacer 218 placedover the assembled upper portion 202 of the conduit 201 which was formedby bonding the first spacer 217 between the first 210 and second 212substrate. To make second spacer 218, one edge of the material is cut tomatch the outer curvature and size of the second substrate 212. Theother edge is cut straight to complete the D-shaped pattern. The openarea that will be necessary for the lower portion 203 of the conduit 201is removed from the second spacer 218 starting at the middle of thestraight edge. The distance between the corners of the opening shouldmatch the width 222 of the main section 120 of the channel to which theconduit is to be attached. The curvature of the opening should alsomatch the inside curvature of the second substrate 212. Note that whenthe second spacer 218 is placed over the assembled upper portion 202 ofthe conduit 201, an opening is present that would allow fluid medium toflow from the upper portion 202 to the lower 203 portion. To completethe construction of the conduit 201, second spacer 218 is aligned andbonded with an appropriate bonding agent or adhesive to the assembledupper portion 202 of the conduit 201. The third substrate 214 (FIG. 7)is then aligned and bonded to the second spacer 218.

When conduit assembly 200 (FIG. 7) is put into operation, fluid mediumand any entrained sample particles enter through small portal 204,travel the length of the conduit 201, and then exit through large portal206. Conduit 201 is designed so that the distance from the small portal204 to any point along the opening of the large portal 206 issubstantially equivalent. The size and shape of the conduit assembly 200may be adjusted to accommodate any size channel from short, narrowmicroscale and lab-on-a-chip type systems to large, wide preparativescale devices. In some alternative embodiments of the conduit assembly200, the bonding agent is eliminated from the construction process.Instead, the parts are held together with fasteners such as screws,bolts, or clamps, or the like. A small quantity of elastomeric sealantis generally applied to spacers 217 and 218 around the perimeter of theconduit 210 to help insure against leakage. The use of fasteners enablesthe conduit assembly 200 to be easily disassembled and cleaned whennecessary. Bonding agents and/or fasteners also provide a means forconnecting the large portal 206 in the conduit 201 to the main section120 of a channel.

Other embodiments of the conduit assembly 200 may be constructed withoutthe use of spacers 217 and 218 to define the conduit 201. Instead, toform the upper portion 202, the triangular-shaped area described abovefor spacers 217 may be machined directly into the curved surface offirst substrate 210 or second substrate 212 at the appropriate location.The depth of the incised area is generally equal to or smaller than thethickness of the main section 120 of the channel to which the conduit201 is to be connected. An area patterned after the cutout section ofspacer 218 (FIG. 8B) may also be machined to a predetermined depth intofirst substrate 210 or third substrate 214 at the appropriate locationto form the lower portion 203 of the conduit 201. The three substrates210, 212, and 214 are then bonded or fastened to construct the conduitassembly 200 as described for FIG. 7.

The construction procedure outline above for FIG. 7 works well for largemicroscale and macroscale conduits assemblies. As the dimensionsdecrease in size to small microscale or nanoscale conduits, however, thefollowing alternative approach may be more applicable. This alternativeapproach is shown in FIGS. 9 and 10A-100. To differentiate thesubstrates employed in this alternative approach from those used in thedescription of FIG. 7, the substrates that comprise the embodiments inFIGS. 9 and 10A-C are designated as substrate A 310, substrate B 312,substrate C 314, and substrate D 316. The distinction is made tofacilitate the description of the different shapes and uses for thesubstrates.

Substrates A 310, B 312, C 314, and D 316 may be composed of a varietyof solid materials including materials that are electrically andthermally conductive, semiconductive, or nonconductive in nature, orvarious composites or combinations thereof. The substrates may besingular entities, layers of the above materials, or materials coveredor coated with liquid or semi-liquid substances. Often, because theembodiments are microfabricated, substrate materials are selected basedupon their compatibility with known microfabrication techniques, e.g.photolithography, wet chemical etching, laser ablation, air abrasiontechniques, LIGA, reactive ion etching, injection molding, embossing,and other techniques. In some preferred aspects, the substrate materialmay include materials normally associated with the semiconductorindustry in which such microfabrication techniques are regularlyemployed. Common materials are silica based substrates such as glass,quartz, or silicon. In other preferred aspects, the substrate may bepolymeric in nature, including such plastics as polymethylmethacrylate(PMMA), polycarbonate, polytetrafluoroethylene, polyvinylchloride (PVC),polydimthylsiloxane (PDMS), polysulfone, and the like. Which eversubstrate is selected, it must also be compatible with the full range ofconditions to which the embodiment may be exposed in its final use.These conditions may include extreme temperatures, pH, and chemicalconcentrations and the application of electric fields. The substratesused in components employed in the fabrication of the embodiment may beof the same material or different.

The embodiment of the conduit assembly 200 shown as an exploded view inFIG. 9 is assembled in and around substrate A 310. For simplicity,substrates A 310, B 312, and C 314 are all shown as rectangular solids.Substrate D 316 is cylindrical in shape. The length of the cylindershould equal the thickness of substrate A 310. The optimal shape anddimensions of the rectangular substrates, however, depend on theultimate use of the embodiment and how it is to be integrated with otherdevices. The equations associated with the model discussed above withFIG. 5 generally provide a useful guide in evaluating and relating thevarious parameters. The critical factors for substrate A 310 are itsthickness and the diameter of the round hole 318 through the face ofsubstrate A 310 to be used to accommodate substrate D 316. The thicknessof substrate A 310, for example, depends on the size of thetriangularly-shaped upper part 202 of the conduit 201 to be used in theconstruction. The height of this upper part 202 in turn depends on thewidth of the channel to be employed and the radius-to-chord ratio (r/c).Using a radius-to-chord ratio of 1.0 with a 250 micrometer wide channel,for example, requires that substrate A 310 be a minimum of 240micrometers thick. The hole 318 for substrate D 316 would be 500micrometers in diameter. Although the location of the hole 318 throughthe face of substrate A 310 is not critical, it is important that thesides be smooth, straight, and perpendicular to the surface of thesubstrate. The hole is generally positioned to accommodate othercomponents or devices.

The main section 120 of the channel to be connected with the conduit 201is incised into substrate B 312. One end of the incised area is roundedto the same diameter as the hole 318 in substrate A 310 to form thelower part 203 of the conduit. An inlet tube 25 (FIG. 12) is incisedinto substrate C 314. To prepare substrate D 316, the triangular upperpart 202 of the conduit is incised into the side of the cylinder. Thebase of the triangle should align with one end of the cylinder. Thedepth of the triangular upper part 202 cut into the cylinder should beuniform and equal to or smaller than the depth of the main section 120of the channel incised into substrate B 312. If the length of thecylinder is greater than the height of the triangular area, an inlettube 25 is incised into the side of the cylinder to connect the smallend of the triangular area to the other end of the cylinder as shown inFIG. 10A.

The embodiment is assembled by bonding substrate A 310 to substrate C314 so that the inlet tube 25 in substrate C 314 aligns with the hole318 in substrate A 310 as shown in FIGS. 10B and 10C. Cylindricallyshaped substrate D 316 is then secured in hole 318 in substrate A 310with the incised upper part 202 of the conduit or inlet tube 25 alignedwith the inlet tube in substrate C 314. To complete the assembly,substrate B 312 is bonded to substrate A and aligned as shown in FIGS.10B and 10C. The method used in bonding and securing the substratestogether depends on the composition of the substrates. Techniquescommonly used in microfabrication include fusion bonding, anodicbonding, adhesive bonding, eutectic bonding, solder bonding, and othersand are familiar to someone knowledgeable in the art.

FIG. 11 shows one embodiment of a path-equalized channel assembly 105formed using two conduit assemblies 200 (FIG. 7) fabricated using asingle first substrate 210. As in the construction in FIG. 7, the upperportion 202 of the conduit 201 is formed between the inner surface ofsecond substrate 212 and the curved surface of first substrate 210. Inthis embodiment, however, two second substrates 212 are placed onopposite sides of a single cylindrical first substrate 210, eachseparated from first substrate 210 by an appropriately shaped andconfigured first spacer 217 (FIG. 8A). For clarity, first spacer 217 isnot shown in FIG. 11. The lower portion 203 of the conduit 201 and themain section 120 of the channel are formed from a single second spacer218 and a single third substrate 214 as shown in FIG. 11. Whenassembled, the lower portion 203 of the conduit 201 stretches only fromthe inner surface of the second substrate 212 to line 208. Line 208represents the dividing point between the large portal 206 (FIGS. 4A and7) of the conduit 201 and the main section 120 of the channel. Together,the two conduits 201 and the main section 120 of the channel constituteone embodiment of a path-equalized channel 100. To facilitate easydisassembly for cleaning and modification, fasteners rather than bondingagents may be used to attach the third substrate 214 during the assemblyof the channel assembly 105.

In operation, the channel assembly in FIG. 11 might be used as part ofan entire system, one that supplies fluid medium and sample material tothe channel assembly and then detects, analyzes, and/or collects thematerial after processing. FIG. 12 shows a simplified schematicrepresentation for such a system. The process might be involved withmanufacturing, for example, or analysis, or material separation andisolation. Fluid medium used in the process generally originates in afluid reservoir 20. From the reservoir, the fluid is forced by a fluidpropulsion mechanism 30 through the channel assembly 105 and finally tothe detector 60 and a fraction collection device 70, if collection isdesired. Sample particles to be processed may be added directly into thefluid reservoir 20 or introduced into the system using an injectiondevice 40 placed typically in inlet tube 25 between the fluid propulsionmechanism 30 and channel assembly 105. For a macro-scale bench-topsystem, a six-port loop injector valve as commonly employed in liquidchromatography is suitable for this purpose, although other means maywork equally well.

The fluid propulsion mechanism 30 in the system may be of any design,but should be able to impel the fluid medium in a constant, pulse-freestream. The flow rate depends on the particular application, but mayvary from as low as 1 nanoliter/second for nano-scale analytical systemsto multiple liters/second in large-scale preparative or manufacturingwork. Syringe, peristaltic, and well-damped reciprocating type pumps arecommon for larger applications. Fluid propulsion techniques employingcentrifugation, pressure, acoustics, or electrokinetics are typical withnano- and micro-scale systems. Flow rate control may be an integral partof the propulsion mechanism 30. To monitor or analyze materials as theyexit from the channel assembly 105, one or more detectors may beincorporated into the system. The detector 60 may be a conventionalliquid chromatography or gel permeation chromatography detector, forexample, such as an ultraviolet/visible absorption detector orfluorescence detector. More specific information about various materialparameters may be gleaned, however, by using a device such as amulti-angle laser light scattering (MALS) detector or one designed toprovide direct chemical analysis such as an inductively coupled plasmaspectrometer coupled directly to a mass spectrometer (ICP-MS). Thedetector 60 is preferably interfaced with a personal computer (notshown) for subsequent data handling and analysis. The computer may alsobe used to automate the injection device 40 and fraction collectiondevice 70, and control the flow rate provided by the fluid propulsionmechanism 30.

To minimize band spreading and loss of resolution once sample materialshave been introduced into the system, low volume inert tubing isgenerally used for all interconnections between components. Thisincludes inlet tube 25 between fluid propulsion mechanism 30 and channelassembly 105, outlet tube 55 joining channel assembly 105 to detector60, and fluid communication line 65 connecting detector 60 to fractioncollection device 70. Many macro-scale applications use PEEK(polyetheretherketone) or stainless steel tubing. In most nano- andmicro-scale systems, the fluid communication lines are engraved directlyin the substrate employed to construct the system. Fluid communicationline 15 between the fluid reservoir 20 and the fluid propulsionmechanism 30 generally need not be low volume.

The design using a single cylindrical first substrate 210 described inFIG. 11 works well with short and/or wide path-equalized channelassemblies 105. For larger and narrower channels 110, a more elongatedfirst substrate 210 may be more appropriate as in the embodiment shownin FIG. 13. The first substrate 210 may be machined to the appropriateshape from a single block of material or fabricated from smallercomponents. FIG. 14A, for example, shows an exploded view of firstsubstrate 210 constructed from two D-shaped sections, cut from acylinder as in FIG. 7, secured to both ends of a rectangular section.The rectangular section may be fabricated from materials or componentsthat may be used in the final channel 100 to produce or assist in theprocess for which the channel assembly 105 is being constructed. Beforeassembling the upper portion 202 of the two conduits 201 in FIG. 13, asmall hole should be made into each second substrate 212 in such a waythat the hole will be located just inside the cut-out triangular area ofthe first spacer 217 when the conduit assemblies 200 are assembled. Thishole, which is the small portal 204 for the conduit 201, should befitted with appropriate tubing to serve as inlet tube 25 or outlet tube55 described in FIG. 12. To assemble, each first spacer 217 (FIG. 8A) isaligned and bonded to the appropriate curved surface of the firstsubstrate 210 with a bonding agent or adhesive and the inner surface ofeach second substrate 212 is then aligned and bonded to first spacer 217using the same procedures as described in FIGS. 7 and 11. Alternatively,by using fasteners rather than bonding agents, the upper portion 202 ofthe conduit 201 may be readily separated from the rectangular section ofthe first substrate 210 and the conduit 201 may be easily disassembledfor cleaning and adjustment.

To complete the construction of the channel assembly 105 in FIG. 13, thesecond spacer 218 is prepared generally having the same thickness asfirst spacer 217 and the shape shown in FIGS. 13 and 14B. An area isremoved from the center of spacer 218 to form the lower portion 203 ofthe conduit 201 and the main section 120 of the channel. The sides ofthe cutout area should be parallel and spaced to equal the distanceacross the opening in the upper portion 202. The curved ends of thecutout area should also match the inside curvature of the secondsubstrate 212. When the second spacer 218 is placed over the assembledupper portion 202 of the conduit 201, an opening should be present thatwould allow fluid medium to flow between the upper portion 202 and thelower 203 portion. The third substrate 214 should be the same size orlarger than the second spacer 218 and of appropriate thickness. As shownin FIGS. 13 and 14B, the general shape of third substrate 214 and secondspacer 218 may be the same. The channel assembly 105 in FIG. 13 iscompleted by aligning and bonding or fastening second spacer 218 andthird substrate 214 to the previously assembled upper portion 202. As inFIG. 11, the lower portion 203 of the two conduits 201 stretches onlyfrom the inner surface of the respective second substrates 212 to line208. Line 208 represents the dividing point between the large portal 206(FIG. 7) of the conduit 201 and the main section 120 of the channel. Thearea between the two lines 208 becomes main section 120 of the channel.Together, the two conduits 201 and the main section 120 form the channel100 within one embodiment of a path-equalized channel assembly 105.

Other embodiments of the invention enable fluid medium and/or samplesparticles to be delivered or collected from a main section 120 of thechannel through multiple portals, side-by-side. For example, FIG. 15shows the main section 120 of the channel connected to a conduit 201that is segmented into three areas and incorporates two small portals204. The design allows sample particles to travel along the center ofchannel 120 shielded from the edges of the channel by parallel flowingstreams of fluid medium. As in the earlier embodiments, the upperportion 202 of the conduit 201 in FIG. 15 is constructed with firstspacer 217 sandwiched between the first 210 and second 212 substrate. Tofacilitate the correct alignment, first spacer 217 is first bonded orfastened to the second substrate 212. Spacer 217 is designed to includetwo narrow partitions 216 that are placed so that they proceed fromeither side of the lower of two small portals 204 in second substrate212 to the bottom of the triangular area as shown in FIGS. 15 and 16A.Once installed on second substrate 212, spacer 217 is aligned and bondedor fastened to first substrate 210. The lower portion 203 of the conduit201 may then be formed using second spacer 218 and third substrate 214as described for FIGS. 7, 11, 13 and 14B.

When conduit assembly 200 in FIG. 15 is placed into operation, sampleparticles entrained in fluid medium will be introduced through the lowersmall portal 204. Fluid medium flowing through the upper small portal204 will wash over the lower small portal 204 and carry the sampleparticles into the main section 120 of the channel. Fluid medium fromthe upper small portal 204 will also flow on the outside of thepartitions 216 forming the parallel flowing streams that will shield thesample particles from the edges of the channel 120. Separate inlet tubes25 from the fluid propulsion mechanism 30 in FIG. 12 may be used tosupply fluid medium to the upper and lower small portals 204 on theconduit 201. The conduit 201 and main section of the channel 120 in FIG.15 are part of the channel assembly shown in FIG. 12. Injection device40 may be incorporated into the inlet tube 25 supplying the lower portal204 in FIG. 12. Either a separate device or a device within the fluidpropulsion mechanism 30 may be used to control the relative flow offluid medium through the two small portals 204. When designed andoperated correctly, no sample particles enter the parallel flow streamsand the flow rate of fluid medium is substantially uniform across thewidth of the main section 120 of the channel.

To accommodate the collection of sample particles at the other end ofthe main section 120 of the channel, a conduit 201 of slightly differentdesign is employed than the one shown in FIG. 15. Although assembled asdescribed above, first spacer 217 here is designed to isolate the fluidmedium containing the sample particles from the parallel flow streamsused to separate the particles from the edges in the main section of thechannel 120. The narrow partition 216 circumscribes the lower smallportal 204 in a way that prevents fluid medium from inside the partitionfrom reaching the upper small portal 204. The arrangement is shown inFIG. 16B. The small portals 204 shown in FIGS. 16A and 16B are not partof first spacer 217. The portals 204 are shown for reference to betterillustrate the positioning of the partitions 216. Fluid from the uppersmall portal 204 leaves the conduit 201 through outlet tube 55 (FIG. 12)to a collection container while the sample particles entrained in thefluid medium exit substantially through the lower small portal and asecond outlet tube 55 to detector 60. Although the use of parallel flowstreams has appeared in prior art to minimize edge effects, the presentembodiments possess two distinct advantages compared with the earlierexamples (Giddings et al., 1984). One, as with other embodiments of thepresent invention, the design in FIG. 15 substantially eliminates bandspreading due to end effects. And two, the present design avoidsdiluting the sample particles with the fluid medium used in the parallelflow.

Another embodiment of the invention enables fluid medium and/or sampleparticles to be delivered to or collected from main section 120 of thechannel through multiple side-by-side small portals. This side-by-sidearrangement may be utilized in two-dimensional systems, for instance,where two processes, generally at 90 degrees to each other, areperformed simultaneously across the channel. Chromatography orfield-flow fractionation could occur in one direction, for example, andelectrophoresis in the other. The cumulative effect of the two processescould cause sample particles to segregate into select aggregates bothdown the length and across the width of the channel. As the particlesare carried by the fluid medium to the end of the channel, multiplesmall side-by-side portals enable the aggregates to be collected andisolated individually. To construct this embodiment, componentsdescribed for FIGS. 14A and 14B may be modified and coupled together asshown in the exploded view in FIGS. 17A and 17B. FIG. 18 provides anillustration of an appropriate first spacer 217. The upper portion 202of the conduit 201 is fabricated with first spacer 217 (FIG. 18)sandwiched between the first 210 and second 212 substrates (FIG. 17A) asdescribed for earlier embodiments. Once assembled, second spacer 218 andthird substrate 214 are attached to form the lower portion 202 of theconduit 201. Appropriate bonding agents and/or fasteners may be used.For the purpose of illustration, FIGS. 17A and 17B show components thatmay be used to construct an embodiment possessing two independent smallportals 204 for introduction of fluid medium and/or sample particlesinto a main section 120 of the channel and two independent small portals204 for collection. The number of introduction and collection smallportals 204, however, need not be equal and may be expanded by simplycoupling additional components together.

In other embodiments, multiple portals are stacked, enabling theisolation and collection of sample particles that have aggregated intoequilibrium zones across the thickness of the main section 120 of thechannel. Such an arrangement is shown in the embodiment in FIGS. 19A and19C, for example, from two different viewpoints. FIG. 19A shows achannel assembly 105 from a perspective perpendicular to fluid mediumflow through the main section 120 of the channel that provides a viewacross the width of the channel 120. FIG. 19C is from the sameperspective but provides a view across the thickness of the main section120. This represents the sectional view from FIG. 19A taken at sectionline 19C-19C. The construction techniques here are similar to thosedescribed above except that additional spacers and substrates arerequired. As in the embodiment shown in FIG. 11, two second substrates212 are placed on opposite sides of a single cylindrical first substrate210, each separated from first substrate 210 by an appropriately shapedand configured first spacer 217 (FIG. 8A). Each second substrate 212contains a small hole to serve as the small portal 204 positioned sothat the hole is just inside the cut-out triangular area of the firstspacer 217 when the conduit assembly 200 is assembled. The configurationof the hole is such that it may be fitted with low-volume tubing throughthe narrow thickness of the second substrate 212 to serve as an inlettube 25 or outlet tube 55 as described for FIG. 12. The thickness ofsecond substrate 212 need only be thick enough to accommodate thedimensions of the tubing.

To provide a second portal 204 to this stacked embodiment shown in FIGS.19A and 19C, another first spacer 217 is wrapped around the previouslyinstalled second substrate 212 followed by another second substrate 212.This process is repeated for each successive portal 204. Each layer issecured with appropriate bonding agents or fasteners. To form the lowerportion 203 of each conduit 201 and the main section of the channel 120,alternating second 218 and third 219 spacers are installed and finallycapped with the third substrate 214 as shown in FIG. 19C. The second 218and third 219 spacers are aligned as shown in FIGS. 19B and 19C with theend of the opening in third spacer 219 generally defining the end of themain section of the channel 120. Line 208 in FIGS. 19A and 19B shows thedividing line between the lower portion 203 of the conduits 201 and themain section of the channel 120.

FIGS. 20A and 20B show embodiments of a conduit assembly 200 that may beused to deliver or collect sample material from a surface or an openvolume. The figures show modified versions of the conduits 201 encircledby the dashed line labeled 20A on the right-hand side of FIG. 19C. Theview, however, is rotated 90 degrees. Also, unlike the embodiment inFIG. 19C, the embodiment in FIG. 20A comprises only a single conduit201. FIG. 20B shows an embodiment that comprises two conduits 201 placedadjacent to each other. Again, unlike the conduits 201 in FIG. 19C thatfunction in association with a process channel 120, the conduits 201shown in FIGS. 20A and 20B empty into or collect from surfaces or openvolumes. The embodiments in FIGS. 20A and 20B are constructed using thesame materials, techniques, and configurations as described above forthe embodiment in FIGS. 19A, 19B, and 19C and described previously forFIG. 7. The principal difference is that sampling strips 230 may berequired to properly align the conduit 201 for sample delivery orcollection. Alternatively, the shape and configuration of the first 210,second 212, and third 214 substrates may be slightly altered to servethe same purpose.

As shown in and described for FIG. 7, the first substrate 210 is aD-shaped solid which can easily be fabricated by cutting a cylindricalsolid from end-to-end. The cut is preferably perpendicular to the endsof the cylinder. The resulting surface should be rendered uniformlysmooth and flat. The second substrate 212 is a crescent-shaped solidfabricated to conform to the curvature of the first substrate 210. Thecrescent-shaped solid is constructed by cutting a tube end-to-end insuch a way that the arc that forms the inside surface of the tube isapproximately the same length as the curved outside surface of the firstsubstrate 210. As in FIG. 7, a small hole is made into the secondsubstrate 212 to serve as the small portal 204 of the conduit 201. Thethird substrate 214 is typically a flat, sheet-like rectangular solid.Preferably, third substrate 214 is shaped to match the D-shapedsilhouette of the first 210 and second 212 substrates when assembled.The shape and characteristics of the first 217 and second 218 spacerswere previously described for FIGS. 7 and 8A-C.

To construct the upper portion 202 of the conduit 201 in FIG. 20A, theinner surface of second substrate 212 is wrapped around and bonded tothe first substrate 210 with an appropriately shaped and configuredfirst spacer 217 in between. To complete the construction of the conduit201, second spacer 218 is aligned and bonded to the assembled upperportion 202 of the conduit 201. The third substrate 214 is then alignedand bonded to the second spacer 218. For ease in disassembly andcleaning when necessary, fasteners may be used in lieu of bonding agentsor adhesives. Sampling strips 230 may be added and configured at the endof the lower portion 203 of the conduit 201 as needed to facilitatefluid medium and/or sample collection or delivery from or to a surfaceor open volume.

FIG. 20B is constructed in much the same fashion. To provide a secondportal 204 to the embodiment shown in FIG. 20A, another first spacer 217is wrapped around the previously installed second substrate 212 followedby another second substrate 212. This layer is again secured withappropriate bonding agents or fasteners. To form the lower portion 203of each conduit 201, the second 218 and third 219 spacers are installedand finally capped with the third substrate 214 as shown in FIG. 20B andsampling strips 230 are affixed. The third 219 spacer is D-shaped and isgenerally designed to extend to and align with the outer edge of thesampling strips 230.

With two adjacent conduits 201, several operational options areavailable for the embodiment. If desired, for example, each conduit 201may be used to deliver a different fluid medium and/or sample materialto a surface or open volume aligned with the sampling strips 230 at theends of the lower portion 203 of the conduits 201. The delivery processmay be either simultaneously or sequentially. The surface or volume maybe stationary or moving relative to the conduit assembly 200.Alternatively, the conduits 201 may be used to collect material from asurface or volume. By employing filters or other selection devices, eachconduit 201 may be directed to collect samples with a differentcharacteristic. Another alternative is to have one conduit 201delivering fluid medium (and possibly entrained material) to the surfaceor open volume and the second conduit 201 collecting fluid medium andmaterial. This process works well when it is necessary to dissolve ordislodge sample material before it can be collected.

Other fabrication techniques and configurations for the conduit may alsobe used. For example, an appropriately programmed CNC milling machinecan easily impart the shape of a conduit 201 into a block of firstsubstrate 210. The principal requirement is that the conduit 201 bedesigned so that the distance from the small portal 204 through theconduit 201 to any position along the opening of the large portal 206 issubstantially equivalent. In essence, the conduit enables the flow offluid medium from a location of small cross-sectional area, the smallportal (possibly a point), to a location of large cross-sectional area,the large portal (possibly represented substantially by a line). Withfew restrictions placed on the shape of the conduit 201, it is oftenconvenient to express the contour of the conduit mathematically. Sincethe distance from a point to a line is not constant in two-dimensionalspace, the conduit can only be visualized and constructed using a thirddimension. For example, the contour may take the form of a surfacegenerated from the arc of a circle between the point and varyingpositions on the line. The length of the arc is kept constant. Only theradius of the circle is varied to accommodate the changingtwo-dimensional distance between the point (small portal 204) and thepositions on the line (large portal 206). Other geometric shapes alsowork well. After using a CNC milling machine to cut out the appropriatecontour in a block of first substrate 210, another piece of firstsubstrate 210 is machined to complement the first piece leaving suitablespace within the shape of the conduit for the passage of fluid medium.The first 210 and second 212 substrates may be bonded together with anappropriate bonding agent or adhesive. Alternatively, the substrates 210and 212 may be joined with appropriate fasteners. The resulting conduitassembly 200 might resemble the embodiment shown in FIG. 21.

The following is a method that may be used for delivering fluid mediumand materials between a first location 226 (FIG. 3) and a secondlocation 228 using the apparatus described above as the presentinvention. The second location 228 may be a process channel, a surface,or an open volume. The method substantially eliminates the end effectsgenerally associated with transferring fluid and entrained materialsfrom a smaller or narrower space to a larger or wider space. Any of themany embodiments may be used.

In a non-limiting exemplary embodiment, as shown in a flowchart in FIG.22, the method preferably comprises five steps: (1) Obtaining aapparatus described as the present invention. (2) Connecting or aligningthe large portal in the conduit as necessary to connect to the mainsection of a channel or align with the desired surface or open volume.(3) Introducing fluid medium into the conduit of the apparatus via itssmall portal until the conduit is filled with the fluid medium. (4)Introducing a sample of material into the fluid medium in the conduit.(5) Introduce additional fluid medium at a predetermined flow rate intothe conduit via its small portal. The fluid medium travels through theconduit and exits by way of the large portal. Since the particles ofmaterial that comprise the sample follow substantially equal lengthpaths through the conduit from the small portal to the large portal, endeffects are substantially eliminated.

A similar method may be used for collecting fluid medium and materialsfrom a second location 228 (FIG. 3) using the apparatus described aboveas the present invention. Again, the second location 228 may be aprocess channel, a surface, or an open volume. This method alsosubstantially eliminates end effects. Any of the many embodiments of theinvention may be used. As shown in a flowchart in FIG. 23, the methodcomprises four steps. (1) Obtaining an apparatus described as thepresent invention. (2) Connecting the large portal in the conduit asnecessary to the main section of a channel or aligning with a desiredsurface or open volume. (3) Introducing fluid medium into the conduit ofthe apparatus via its large portal until the conduit is filled with thefluid medium. (4) Collecting any additional fluid medium and anyentrained materials entering by way of the large portal of the conduit.The fluid medium and materials then travel through the conduit and exitby way of the small portal. Again, since the material particles thatcomprise the sample follow substantially equal length paths through theconduit from the large portal to the small portal, end effects aresubstantially eliminated.

The steps in the above two methods may be expanded, combined, and/ortheir order changed to accommodate the requirements of the specificsample, application, and/or embodiment of the apparatus employed.Greater detail and alternative versions of the methods are given below.The methods should be familiar to one skilled in the general art ofmoving fluid media and entrained materials between locations ofdifferent dimensions.

Under normal operating conditions, the conduits and main section of theprocess channel are prefilled with fluid medium by pumping the fluidmedium, as described for FIG. 12, from a fluid reservoir 20, through aninjection device 40, and into the channel assembly 105 where theconduits and channel are located. If the conduit is to be used todeliver fluid medium and materials to a surface or open volume, nochannel would be present. Fluid medium would be prefilled as above butonly up to the large portal of the conduit. It may be necessary to freethe liquid fluid medium of dissolved gases to prevent the formation ofbubbles in the channel due to outgassing. Once the conduits and channelare filled, the injection device 40 is used to insert the sampleparticles into the channel assembly 105 as fluid medium continues toflow at an appropriate flow rate. Conditions appropriate for the processare then applied to the channel or the conduits and the channel.Alternatively, the order may be switched; the appropriate processconditions may be initiated before the introduction of the sample. Forsome applications, it may be desirable to use a stop-flow technique toprovide sufficient time for sample processing before resuming fluidmedium flow. Other considerations may also be important if the conduitis to be used to deliver fluid medium and materials to a surface or openvolume.

Sample volumes and concentrations depend on the application and thedesign of the apparatus. Care, however, needs to be taken and themethods and apparatus may require alteration to avoid excessivespreading of the band of sample particles when the apparatus is usedparticularly with some techniques. Field-flow fractionation (FFF), forexample, would be one such technique. Above a certain point, separationresolution in FFF can become a function of the size of the sample. Thesteady state equilibrium zones that form in the channel during theseparation process are three-dimensional in nature with a breadth(across the thickness of the channel), a width (across the width of thechannel), and a span (along the length of the channel). Increasing thevolume of the sample generally also increases the span of each zone. Thebreadth is restricted by the balancing of opposing equilibrium forces.Ultimately, if the sample becomes large enough, the zones stretch fromone end of the channel to the other. There is no differentiation of thezones along the length of the channel. Resolution of the zones is thenonly possible across the thickness direction of the channel. To isolatethe individual zones, a different conduit (and detector) must beprovided for each zone. For example with five zones, one conduit couldbe used to introduce the sample into the channel, but five conduits (onefor each zone) stacked across the thickness of the channel would berequired to collect the separated particles. The method would also haveto be modified to reflect the fact that the zones are collectedsimultaneously rather than one at a time. Similar alterations to themethod would be necessary if two-dimensional techniques were used asdiscussed earlier, but the multiple conduits would be installedside-by-side.

While exemplary embodiments of the invention have been described, itshould be apparent that modifications and variations thereto arepossible, all of which fall within the true spirit and scope of theinvention. With respect to the above description then, it is to berealized that the optimum relationships for the components, includingvariations in order, form, content, function, and manner of operation,are deemed readily apparent and obvious to one skilled in the art, andall equivalent relationships to those illustrated in the drawings anddescribed in the specification are intended to be encompassed by thepresent invention.

The above description and drawings are illustrative of modificationsthat can be made without departing from the present invention, the scopeof which is to be limited only by the following claims. Therefore, theforegoing is considered as illustrative only of the principles of theinvention. Further, since numerous modifications and changes willreadily occur to those skilled in the art, it is not desired to limitthe invention to the exact construction and operation shown anddescribed, and accordingly, all suitable modifications and equivalentsare intended to fall within the scope of the invention as claimed.

ADVANTAGES AND RAMIFICATIONS

Non-limiting exemplary embodiment(s) of the present disclosureprovide(s) apparatus(es) and methods for the uniform transference offluid media and any entrained materials or samples to and from differentlocations possessing different cross-sectional areas with a minimum ofband spreading and dispersion. As a non-limiting example, what makes thecurrent invention unique is that it almost completely eliminates endeffects and provides simple and expandable apparatuses and methods thatmay be used with locations as diverse as enclosed channels, surfaces, oreven open volumes.

Non-limiting exemplary embodiment(s) of the present disclosure may becentered around a specially designed conduit that provides substantiallyequal paths from a small portal at one end of the structure to a largeportal at the other end. Despite the fact that numerous devices andstudies were published throughout the 1980s, 1990s, and early 2000s, noother apparatus or methodology to date essentially eliminates the flowand path irregularities associated with end effects. Often the partialsuccess of prior art came at the expense of dramatically increasing thecomplexity of the instrumentation or its fabrication. Even the inventorsof these alternatives rarely use their own inventions. By providing asimple, easily constructed and disassembled uniform path-length conduit,the present invention furnishes a means that substantially eliminatesend effects, significantly improves sample separation resolution, andyet is facilely maintained, adjusted, or replaced. Non-limitingexemplary embodiment(s) of the present disclosure may be effectivelyincorporated into almost any size system from “lab-on-a-chip” microscaleinstrumentation to process channels designed for preparative work on amanufacturing scale.

The advantages of non-limiting exemplary embodiment(s) of the presentdisclosure are significant.

1. The apparatuses and methods substantially eliminate the sample bandspreading associated with end effects that traditionally contribute tothe loss of sample resolution as fluid medium is transitioned from asmaller or narrower space to one that is larger or wider.2. Design of the apparatuses and methods may be easily adapted todeliver or collect fluid medium and sample materials to or from aprocess channel, a surface, or an open volume of any size and used foralmost any purpose.3. When used in association with a process channel, the channel may beemployed for a wide variety of applications. Examples include themodification and/or synthesis of chemicals or materials, the separationof mixtures including clinical and environmental samples, and thedetection and/or characterization of particles and/or substances.4. The simplicity of the apparatuses lends themselves to a wide varietyof fabrication techniques. Components of the apparatuses may bepermanently assembled with appropriate bonding agents or provisionallyfastened to facilitate occasional cleaning, repair, or replacement.5. The apparatuses and/or any associated channel or open volume may beunfilled with any material or the apparatuses and/or any associatedchannel or open volume may be filled with a gel, or filled with porous,granular, or particulated material.6. The apparatuses may be segmented to allow sample material to travelalong the center of a subsequent channel shielded from the edges of thechannel by parallel flowing streams of fluid medium. The shieldingminimizes edge effects, another process that can contribute to loss ofsample resolution. Upon exiting the channel, the sample particles may becollected separately from the parallel flowing streams to avoidunnecessary dilution of the sample.7. The apparatuses and methods may be expanded to accommodate multipleconduits, either side-by-side or stacked, permitting multiple inletand/or outlet connections to a single separation channel. Thesemodifications are particularly valuable in large-scale samplepreparative separations and where two-dimensional techniques areemployed.

What is claimed as new and what is desired to secure by Letters Patentof the United States is:
 1. An apparatus for transferring fluid mediumand materials with a minimum of band spreading and dispersion due tonon-equal path-lengths between a first location and a second location,each possessing a different cross-sectional area, comprising: a firstconduit of a predetermined shape having a first portal of predeterminedsize and a second portal of predetermined size, said first conduitfurther having a path formed therein, said predetermined shape of saidfirst conduit being such that a length of said path through said firstconduit from said first portal to anywhere within said second portal issubstantially the same; means for moving said fluid medium and particlesinto or out of said first portal in said first conduit from or to saidfirst location; and means for conveying said fluid medium and particlesto or from said second portal in said first conduit from or to saidsecond location; wherein said predetermined size of said first portal issmaller than said predetermined size of said second portal.
 2. Theapparatus according to claim 1, wherein said conduit comprises: aplurality of said first portals.
 3. The apparatus according to claim 1,wherein said conduit comprises: a plurality of said second portals. 4.The apparatus according to claim 1, wherein said conduit comprises: aplurality of partitioned sections.
 5. The apparatus according to claim1, further comprising: at least a second conduit having a third portaland a fourth portal, wherein said third portal has a predetermined sizesmaller that a predetermined of said fourth portal.
 6. The apparatusaccording to claim 1, wherein said means for moving said fluid mediumand materials into or out of said first portal in said first conduitfrom or to said first location comprises: one of an inlet tube, anoutlet tube and a combination of said inlet and outlet tubes.
 7. Theapparatus according to claim 1, wherein said means for conveying saidfluid medium and materials to or from said second portal in said firstconduit from or to said second location comprises: one of a connectionof said second portal to or with said second location, and an alignmentof said second portal to or with said second location
 8. The apparatusaccording to claim 1, wherein said first location has one of an open andenclosed volume.
 9. The apparatus according to claim 1, wherein saidfirst location is a surface.
 10. The apparatus according to claim 1,wherein said second location has one of an open and enclosed volume. 11.The apparatus according to claim 1, wherein said second location is asurface.
 12. The apparatus according to claim 1, further comprising: agelatinous, porous, granular, or particulated material disposed withinsaid first conduit.
 13. A method for transferring fluid medium andmaterials with a minimum of band spreading and dispersion due tonon-equal path-lengths between a first location and a second location,each possessing a different cross-sectional area, comprising: obtainingan apparatus, which said apparatus comprising a conduit of apredetermined shape having a first portal of predetermined size and asecond portal of predetermined size, said conduit further having a pathformed therein, said predetermined shape of said conduit being such thata length of said path through said conduit from said first portal toanywhere within said second portal is substantially the same, whereinsaid predetermined size of said first portal is smaller than saidpredetermined size of said second portal; performing one of thefollowing steps connecting said second portal in said conduit to or withsaid second location, and aligning said second portal in said conduit toor with said second location; obtaining and introducing said fluidmedium into said conduit via said first portal until said conduit isfilled with said fluid medium; obtaining and introducing a samplematerial into said fluid medium via said first portal of said conduit;and obtaining and introducing additional fluid medium at a predeterminedflow rate into said conduit via said first portal, wherein said fluidmedium travels through said conduit and exits to said second location byway of said second portal of said conduit; wherein said sample materialand said fluid medium are introduced into said first portal of saidconduit, each traveling through said conduit and being distributedacross said second portal following paths of substantially equal lengththrough said conduit from said first portal to said second portal,thereby substantially eliminating end effects.
 14. A method fortransferring fluid medium and materials with a minimum of band spreadingand dispersion due to non-equal path-lengths between a second locationand a first location, each possessing a different cross-sectional area,comprising: obtaining an apparatus, which said apparatus comprising aconduit of a predetermined shape having a first portal of predeterminedsize and dimensions and a second portal of predetermined size anddimensions, said conduit further having a path formed therein, saidpredetermined shape of said conduit being such that a length of saidpath through said conduit from said first portal to anywhere within saidsecond portal is substantially the same, wherein said predetermined sizeof said first portal is smaller than said predetermined size of saidsecond portal; performing one of the following steps connecting saidsecond portal in said conduit to or with said second location, andaligning said second portal in said conduit to or with said secondlocation; obtaining and introducing said fluid medium into said conduitvia said second portal until said conduit is filled with said fluidmedium; collecting any additional fluid medium and any entrainedmaterials entering by way of said second portal of said conduit, whereinsaid fluid medium travels through said conduit and exits by way of saidfirst portal of said conduit; and wherein said entrained materials andsaid additional fluid medium are collected from across said secondportal and each, traveling through said conduit to said first portal,following paths of substantially equal length through said conduit,thereby substantially eliminating end effects.